Abstract: A nuclear fusion reactor requires a radiation-hardened sensor readout integrated circuit (IC), whose operation should be tolerant against harsh radiation effects up to MGy or higher. This paper proposes radiation-hardening circuit design techniques for an instrumentation amplifier (IA), which is one of the most sensitive circuits in the sensor readout IC. The paper studied design considerations for choosing the IA topology for radiation environments and proposes a radiation-hardened IA structure with total-ionizing-dose (TID) effect monitoring and adaptive reference control functions. The radiation-hardened performance of the proposed IA was verified through model-based circuit simulations by using compact transistor models that reflected the TID effects into complementary metal–oxide–semiconductor (CMOS) parameters. The proposed IA was designed with the 65 nm standard CMOS process and provides adjustable voltage gain between 3 and 15, bandwidth up to 400 kHz, and power consumption of 34.6 µW, while maintaining a stable performance over TID effects up to 1 MGy.